Bayraktar Erol Can, Aung Phyu P, Gill Pavandeep, Shen Guomiao, Vasudevaraja Varshini, Lai Zongshan, Chiriboga Luis, Ivan Doina, Nagarajan Priyadharsini, Curry Jonathan L, Torres-Cabala Carlos A, Prieto Victor G, Jour George
Department of Pathology and Dermatology, NYU Langone Medical Center, New York, New York, USA.
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
J Cutan Pathol. 2025 Apr;52(4):309-316. doi: 10.1111/cup.14782. Epub 2025 Jan 6.
Digital papillary adenocarcinoma (DPAC) is a rare but aggressive cutaneous malignant sweat gland neoplasm that occurs on acral sites. Despite its clinical significance, the cellular and genetic characteristics of DPAC remain incompletely understood.
We conducted a comprehensive genomic and transcriptomic analysis of DPAC (n = 14) using targeted next-generation DNA and RNA sequencing, along with gene expression profiling employing the Nanostring Technologies nCounter IO 360 Panel. Gene expression in DPAC was compared to that in hidradenoma (n = 10). Immunohistochemistry was employed to validate gene expression.
Two out of eight DPACs showed fusion gene rearrangements (CRTC3::MAML2 and TRPS1::PLAG1). No uniform mutational signature was detected in DPAC. Comparative gene expression analysis revealed an enrichment of genes related to matrix remodeling, metabolism, and DNA damage repair. Hallmark pathway analysis demonstrated significant upregulation of E2F target genes in DPAC compared to hidradenoma (p = 0.00710). Human papillomavirus-42 was found to be positive in all of our tested DPAC cases. Immunohistochemistry confirmed increased protein expression of CD56, CDC20, and SOX10 in DPAC. Notably, most DPAC tumors also exhibited B-cell infiltration, as indicated by CD20 staining.
Our findings reveal novel fusions and validate altered replication pathways related to HPV42 in DPAC.
指状乳头状腺癌（DPAC）是一种罕见但侵袭性强的皮肤恶性汗腺肿瘤，发生于肢端部位。尽管其具有临床意义，但DPAC的细胞和遗传特征仍未完全明确。
我们使用靶向新一代DNA和RNA测序对14例DPAC进行了全面的基因组和转录组分析，并采用Nanostring Technologies nCounter IO 360 Panel进行基因表达谱分析。将DPAC中的基因表达与10例汗腺腺瘤中的基因表达进行比较。采用免疫组织化学法验证基因表达。
8例DPAC中有2例显示融合基因重排（CRTC3::MAML2和TRPS1::PLAG1）。在DPAC中未检测到一致的突变特征。比较基因表达分析显示与基质重塑、代谢和DNA损伤修复相关的基因富集。特征通路分析表明，与汗腺腺瘤相比，DPAC中E2F靶基因显著上调（p = 0.00710）。在我们所有检测的DPAC病例中，人乳头瘤病毒42均呈阳性。免疫组织化学证实DPAC中CD56、CDC20和SOX10的蛋白表达增加。值得注意的是，CD20染色显示大多数DPAC肿瘤也有B细胞浸润。
我们的研究结果揭示了DPAC中的新型融合基因，并验证了与HPV42相关的复制途径改变。
